1. Field of the Invention
The present invention relates to the discovery that bacterial vaginosis (BV) can be treated by administering DNase alone or together with antibiotics that are known to treat BV.
2. Description of the Related Art
BV is the most common vaginal infection worldwide and is associated with significant adverse consequences including and preterm labor and delivery (40, 41), post-partum endometritis, (42) and an increased risk of HIV acquisition. (43-45). Reported prevalence rates range from 10-40% depending upon the population studied. (46). However, suboptimal methods of diagnosis and a high percentage of asymptomatic patients make the true prevalence of BV difficult to ascertain. Gardnerella vaginalis (G. vaginalis), is a bacterial species associated with BV.
The pathogenesis of BV remains poorly understood. It is most commonly defined as a pathological state characterized by the loss of normal vaginal flora, particularly species of H2O2-producing species of Lactobacillus, and overgrowth of other microbes including G. vaginalis, Mobiluncus species, and Mycoplasma hominis. Recent data however, suggest a primary role for G. vaginalis as a specific and sexually transmitted etiological agent in BV, as was initially postulated by Gardner and Dukes in 1955. (47-49).
Alterations of both local host immunity and the genital tract microflora appear to contribute to the pathogenesis of BV (39), which can be difficult to eradicate even using targeted antimicrobial therapy (4). In addition, randomized trials of antibiotics for the prevention of BV-associated preterm birth have not shown consistently beneficial effects, suggesting that host inflammatory responses set in motion early in the course of the disease may contribute significantly to the consequences of infection (26, 27).
In the 1950s, Leopold (25) and then Gardner and Dukes (14) observed abundant small, pleomorphic gram-variable rods in the genital tract of women with BV. This organism, first called Haemophilus vaginalis (13) and repeatedly renamed as more information about its characteristics became available (reviewed in (5)), is now classified as G. vaginalis, the sole member of the genus Gardnerella (16, 30). Phylogenetic analysis based on 16S rRNA places Gardnerella in the gram-positive family Bifidobacteriales. An abundance of G. vaginalis and a paucity of Lactobacillus species are characteristic of a BV-associated microflora. G. vaginalis is present in essentially all cases of BV but can also be detected in a minority of asymptomatic women (1). Likewise, several groups have demonstrated that the vaginal microflora is exceedingly complex in BV where the vaginal mucosa is host to many non-Gardnerella organisms (12, 18, 20); however, recent studies have provided additional evidence for G. vaginalis as the primary etiologic agent of BV. (61-63; 78).
BV is exceedingly common, especially in Africa where more than 50% of women in numerous trials, (including the recent trial of acyclovir for HSV suppression in Tanzania) were infected with BV. BV has been repeatedly associated with both increased risk of HIV acquisition and increased viral shedding among those already infected with HIV. In vitro treatment of HIV-infected cells with Gardnerella leads to increased production of HIV viral transcripts.
BV, a chronic infectious/inflammatory disease associated with preterm birth, is strongly linked with the mucosal overgrowth of G. vaginalis and its attachment to epithelial cells. (78). BV has also been referred to in the literature as bacterial vaginosis, non-specific vaginitis, non-specific vaginosis, and bacterial vaginitis; and G. vaginalis has been called Haemophilus vaginalis and Corynebacterium vaginale. BV is caused by a profound shift in the bacteria colonizing the vagina, with overgrowth of a variety of species, most prominently G. vaginalis. During BV, the epithelial surface is covered with a dense collection of G. vaginalis in a biofilm that is frequently recalcitrant to treatment. Even in women for BV with oral or intravaginal antibiotics, the rate of recurrence approaches 50% at 6 months.
Therefore, there is a great need for a new methods and compositions to treat and prevent G. vaginalis infections and BV, with benefits of reducing preterm delivery and minimizing the risk of transmitting HIV from person to person, particularly from an HIV-positive mother who has BV or a G. vaginalis infection to a fetus or an infant during delivery.